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Low Oxygen Preserves Usefulness of Stem Cells


New Haven, Conn. — Low levels of oxygen, or hypoxia, may help preserve the unique undifferentiated nature of stem or progenitor cells, according to a report by Yale School of Medicine researchers in the Journal of Biological Chemistry.

Stem cell therapy is a possible future approach for the treatment of cancer and other genetic diseases. However, it is difficult to maintain the biological functions of stem cells and progenitor cells in culture. Both stem cells and progenitor cells can give rise to mature functional cell types. Progenitor cells, also called precursor cells, are derived from stem cells, but can only produce a more limited number of mature cell types.

Zhong Yun, senior author of the study and assistant professor of therapeutic radiology, said the research could facilitate the use of these cells in future stem cell therapies by leading to improved conservation methods. “Once we know how the microenvironment regulates the functions of stem and progenitor cells, we can potentially protect them from premature differentiation or find ways to mobilize these cells for tissue repair and/or regeneration,” he said.

The “stem cell niche” is a unique tissue microenvironment within cellular tissues that regulates the self-renewal and differentiation of stem cells. Although several contributing structural cell types and molecular pathways have been identified, the microenvironment of the stem cell niche remains largely unclear.

Hypoxia can occur in humans under both normal and pathological conditions, especially in patients with certain types of respiratory disorders, cardiovascular diseases, or cancer. When levels of oxygen are low, mammals increase the expression of a wide variety of genes involved in the production of red blood cells, formation of blood vessels, increased uptake and metabolism of glucose, as well as genes that regulate cell fate.

In this study, Yun and his team used fat precursor cells, or preadipocytes, as a model to investigate the effects of hypoxia on the maintenance of the precursor phenotype. Fat precursor cells can be converted to mature fat cells when treated with a mixture of fat cell-stimulating hormones under normal cell culture conditions. However, under hypoxic conditions, these precursor cells can no longer be converted to mature fat cells.

The research team found hypoxia does not permanently change the ability of these fat precursor cells to become mature. “Rather, hypoxia maintains these fat precursor cells in an undifferentiated progenitor state,” Yun said.

Co-authors include Qun Lin and Yi-Lang Lee of Yale.

Journal of Biological Chemistry 281: 30678-30683 (October 13, 2006)


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